The PerturbFate platform allowed for the identification of common regulatory mechanisms among different cancer mutations. This could aid in the development of new treatment methods for resistant tumors.
Researchers have determined that hundreds of different genetic mutations in cancer ultimately depend on a single common mechanism for cell survival. The results of the study are published in the journal Nature.
Many serious diseases, including oncology, are associated with a large number of genetic disorders affecting various biological processes. Because of this, developing a separate drug for each mutation is virtually impossible. Therefore, scientists have been trying for many years to find universal 'control nodes' through which several mechanisms of disease development pass.
In the new study, specialists created a platform called PerturbFate. The system allows real-time tracking of how genetic changes restructure cell function and identifies key points on which numerous mutations depend.
To test the technology, researchers used chemotherapy-resistant melanoma cells. The scientists sequentially disabled 143 different genes and observed how the behavior of tumor cells changed. At the same time, the platform analyzed DNA availability and the process of synthesizing new RNA in each individual cell, separating old molecular signals from new ones.
The data obtained allowed for the construction of detailed gene regulation maps. It turned out that a wide variety of mutations ultimately lead the cell to the same mechanism — the operation of a mediator complex that helps the tumor survive and resist drugs.
All resistance pathways ultimately converged on a single molecular signal, VEGFC. When the researchers deliberately blocked this node, melanoma cells quickly lost their resistance to therapy and ceased to grow.
The authors of the study believe that this discovery could be an important step toward creating universal treatment methods for aggressive forms of cancer. Instead of developing separate drugs for each mutation, scientists propose targeting the common survival mechanism of the tumor, on which hundreds of genetic changes depend.
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